B9

B9 (Folic acid, Dihydrofolic acid, Folinic acid)

Vitamin B9 is commonly referred to as folic acid. Most individuals who have conceived are familiar with vitamin B9. Physicians often recommend vitamin B9 to females who are trying to conceive and who are pregnant. Studies have shown that vitamin B9 reduces the risks of birth defects in infants if consumed by the mother before and during pregnancy. Since neural tube development occurs during the first month, women should consume a considerable amount of folate during conception.

Vitamin B9 is water soluble. The body utilizes folate to synthesize and repair DNA. Therefore, it plays a vital role in the cell division process. The vitamin also aids in the production of red blood cells and white blood cells. Vitamin B9 deficiencies may prompt a reduced production of white and red blood cells. A low blood cell count is referred to as anemia. Anemia manifests in the body as fatigue, weakness and inability to concentrate.

Recommended Daily Allowances

The recommended daily allowances for folic acid are 400 micrograms for men and women who are not pregnant or trying to conceive. Experts recommend 600 micrograms of folic acid for pregnant women.

Sources of Vitamin B9

While most pregnant mothers will receive folic acid through a supplement, individuals may also find vitamin B9 in a host of natural foods. Many experts recommend natural sources of vitamin B9 because it is easier for the body to absorb. Synthetic vitamins are more difficult to absorb.

Vitamin B9 is most commonly found in the following sources:

Leafy Green Vegetables

Spinach

Asparagus

Romaine Lettuce

Dried or Fresh Beans

Peas

Beer

Pasta

Cereal

Bread

Sunflower Seeds

Orange Juice

Pineapple Juice

Cantaloupe

Honeydew melon

Grapefruit Juice

Banana

Raspberry

Grapefruit

Strawberry

Beets

Broccoli

Corn

Tomato Juice

Bok Choy

Liver

Baker’s Yeast

Dried Cereals

History of the Vitamin

Scientists, in the early 1900s, noticed that a deficiency of folate presented itself in the form of anemia. Dr. Lucy Wills demonstrated that anemia could be alleviated through the consumption of brewer’s yeast. She sought to prove this finding to eliminate anemia during pregnancy. In the 1940s, folate was isolated and extracted from spinach leaves. In the mid 1940s, folate was isolated in crystal form by scientist, Bob Stokstad, under the supervision of Dr. Yellapragada Subbarao. This research occurred at the Lederley Lab in Pearl River, NY.

This research later led to the production of the anti-cancer drug known as antifolate Aminopterin. This research was conducted under the guidance of Dr. S. Farber in 1948. Scientists discovered the role of folate in neural tube development in the 1960s. In the 1990s, scientists pushed for inclusion of the vitamins in foods to assist individuals in meeting their daily allowances for defects. They accomplished this goal through the folic acid fortification program. Most of the fortification in the United States and other countries occurred through breads and cereals.

Health Benefits

Vitamin B9 plays a significant role in the neural tube development of an unborn fetus. The neural tube forms during the first 4 to 6 weeks of pregnancy. Pregnant mothers are recommended to consume between 600 to 800 micrograms to avoid neural damage and birth defects.

Studies have shown that a diet consisting of 5 to 27 micrograms of folic acid per week will assist in the fight against rheumatoid arthritis.

Patients suffering from diabetes mellitus typically have lower levels of folic acid present in the blood. These individuals may also benefit from folic acid supplements or foods fortified with folic acid.

Folic acid may prove beneficial in fighting some cancers. Studies have shown benefits of folic acid in fighting colorectal cancers and breast cancers. The findings are inconclusive. More studies must be conducted to prove the findings conclusively.

Vitamin B9 is also beneficial in fighting certain heart disease. Folic acid has been known to lower homocysteine levels. Elevated homocysteine levels indicate low vitamin B9 levels. Elevated levels may encourage blood cells to stick together and form clots. A blocked artery may cause a heart attack or stroke.

Ailments from Vitamin B9 Deficiencies

Several problems may occur if the body does not receive the daily allowance of vitamin B9. Deficiencies in Vitamin B9 can lead to the following health problems:

Birth Defects

Pregnant women who do not consume between 600 and 800 micrograms of folic acid per day put their unborn fetus at risk for improper development of the brain, skull, and spinal cord. Risk also increases for low infant birth rate, retardation of fetal growth, and pre-term delivery.

Additionally, when homocysteine levels rise in the blood due to low folate levels, pregnant women are more at risk for spontaneous abortion, placental abruption and preeclampsia. During the first four weeks of pregnancy, most women do not even realize that they are pregnant.

Therefore, it is important to maintain a diet rich in folate if there is a possibility of conception. Neural tube defects will ultimately manifest as a spine defect in an infant. Spine defects are often referred to as spina bifida. Brain defects may also occur. The brain defects are referred to as anencephaly. Folic acid supplements also have been shown to reduce the risk of cleft lip, limb defects, urinary tract anomalies, and congenital heart defects. Women who take folic acid supplements reduce the risk of birth defects by 3.9 times.

Alternatively, a recent study by University of Adelaide showed that pregnant mothers who consumed excessive amounts of folic acid during the last trimester of pregnancy may increase the chances of the child developing childhood asthma by 30 percent.

Cancer

A deficiency in Vitamin B9 may lead to problems during DNA synthesis. These problems may cause the DNA to accelerate the growth of cancerous cells instead of normal cells. Colon cancer or colorectal cancer is most often associated with folate intake. Folic acid intake appears to decrease the development of colorectal cancer.

Folate accelerated prostate cancer by 67 percent in those individuals who had a progressive case of cancer. These findings were a result of a European study with 520,000 men participating. Another study showed that 1 mg of folic acid was found to increase the risks associated with prostate cancer. Scientists speculate that this phenomenon occurred because of folic acid’s role in nucleotide synthesis and promotion of cell growth and division.

When cancer is present, folic acid may promote the division and growth of those cells as well. Folate receptors increase during cancer. Folic acid also plays a role in “DNA methylation” in cancer development. Folic acid deficiency inhibits the production of cytosine methylation in DNA. When the production ceases, proto-oncogenes become active and malignant cells begin to form in the body and more specifically, the prostate. The entire process increases the risk for cancer. More studies should be conducted before these findings are conclusive.

Other studies show that diets high in folate also increased the risk for leukemia in children. More studies should be conducted to conclusively prove this finding.

The findings for the effects of folic acid intake on breast cancer reduction are inconclusive. One Swedish study suggests that diets high in folate result in a decreased development of breast cancer. Other studies refute this finding. More studies must be conducted to prove the findings conclusively.

Heart Disease

Studies indicate that homocysteine levels are an indicator or risk factor of heart disease. Experts speculate that high levels of homocysteine may damage arteries or form blood clots that contribute to heart related problems. The data is not conclusive that vitamin B9 will lower homocysteine production and thus, reduce the risk of heart disease. However, the risks of heart disease decreased by 15 percent since the new folate regulations were introduced in the 1990s. Scientists estimate that 13,500 coronary-related deaths are associated with folate deficiencies.

Folate Deficiencies

Deficiencies in folic acid may lead to diarrhea, confusion, anemia, depression, and glossitis. Scientists suggest that increase homocysteine levels may indicate an anemia or decreased folic acid consumption. Individuals who have problems absorbing the vitamin may choose to take a supplement to replenish the presence of vitamin B9 in the body. Patients with celiac disease often have a problem with absorption and may develop a folate deficiency. Obese people who have a Body Mass Index (BMI) of 50 or more may also develop a folate deficiency.

Elderly Population

The results from studies regarding elderly populations and folic acid are mixed. One major concern is the ability of the vitamin B9 to mask a deficiency in vitamin B12 levels. Experts recommend consuming vitamin B9 in conjunction with vitamin B12 to avoid such masking issues. In a study of 747 elderly subjects, experts found that vitamin B9 reduced the risk of heart disease and lowered the homocysteine levels. Each of the subjects consumed 140 micrograms of folic acid per 100 grams of grain product.

The subjects ranged in age from 67 to 96. Because of this study and similar studies, Canada fortifies its food supply with 150 micrograms of folic acid per 100 grams of grain. Much of their elderly population also consumes 400 micrograms. Experts recommend not consuming over the Recommended Daily Allowance (RDA).

Folic Acid Supplements and Vitamin B12 Masking

Experts are often concerned about the consumption of vitamin B9 without vitamin B12. The concern arises because vitamin B9 can alleviate anemia symptoms that are a result of a vitamin B12 deficiency. However, vitamin B9 does not address the deficiencies in the nervous system that result from a vitamin B12 deficiency. Experts grow concerned because although the patient may feel better after taking folic acid, they still may experience nerve damage from a vitamin B12 deficiency.

Patients should not exceed 1000 micrograms or 1 mg of folic acid per day to avoid masking the symptoms associated with a vitamin B12 deficiency. Canadian studies show that no conclusive evidence indicates that high folic acid levels mask vitamin B9. However, more studies must be conducted to determine the effectiveness. In the elderly population, studies have shown that high folic acid levels in conjunction with low vitamin B12 levels promoted “significant cognitive impairment.” The elderly should consult with a physician prior to beginning a vitamin B9 or B12 regimen.

Bone Health

Elevated homocysteine levels related to a folic acid deficiency may lead to osteoporosis, reduction in Bone Mass Density (BMD) and bone fractures. The results are not conclusive and more studies must be done to prove the findings conclusively.

Menopause

Postmenopausal women who consume folic acid supplements may find relief from related symptoms, such as hot flashes. Folic acid is thought to interact with neurotransmitters in the brain, specifically norepinephrine and serotonin, to reduce the effects of hot flashes.

Infectious Disease

Folic acid deficiencies are linked to Plasmodium flaciparum malaria. This type of malaria is linked to anemia. Areas where malaria is endemic, such as Columbia, could benefit from folic acid consumption.

Depression

Some studies link folic acid to a reduction in depression. Studies are not conclusive. More data must be collected to prove this assumption.

Memory

In a study of over 800 people, scientists measured short term memory, mental agility and verbal fluency. During this study, scientists found improved concentration and memory in those individuals over the age of 50 who consumed 800 micrograms or more of folic acid daily. Folic acid is important for cells to divide. Cancer cells divide rapidly. Those who want to curb cancer growth should not consume high amounts of folic acid.

Obesity

Obese patients who consume folic acid may increase the presence of lipolysis in adipocytes. This process may prevent obesity and Type 2 diabetes. Folic acid may also play a role in lowering the accumulation of cholesterol in the liver and in the blood by increasing bile production.

Stroke

Studies have shown that patients at risk for a stroke have decreased their chances of having a stroke by consuming folic acid. Experts found that a folic acid supplement of 5 micrograms per day significantly reduced pulse pressure. Pulse pressure is an indicator of stroke risk.

Parkinson’s Disease

Patients suffering from Parkinson’s disease may benefit from a folic acid supplement. Studies have shown that folic acid lowers homocysteine levels. Elevated homocysteine levels contribute to bone loss and a host of other problems. Additionally, patients suffering from Parkinson’s disease may take a drug known as levodopa. Levodopa is a psychoactive drug taken to treat Parkinson’s disease. The drug may also decrease Bone Mass Density (BMD). Experts have cited improvements in femur bones and lumbar spine as a result of increased Vitamin B9 intake.

Renal Disease

Folic acid supplements have been found to reduce the risk of developing renal diseases in children. Microalbuminuria is a common childhood renal disease associated with a folic acid deficiency.

Macular Degeneration

Several studies have been conducted and documented in a journal article entitled, “Women’s Antioxident and Folic Acid Cardiovascular Study” regarding folic acid and the developmental risks of age-related macular degeneration. These studies found that patients who consumed a folic acid supplement, along with pyridoxine and cyanocobalmin, reduced their risk of developing macular degeneration by 34 percent.

Antifolates

Experts recommend folic acid to promote cell growth and division. Cancer cells characteristically grow fast and divide rapidly. Cancer patients are given drugs to counteract folate metabolism. Antifolate methotrexate is a drug used to treat cancer. It is given to the patient to inhibit the production of the active for of THF from dihydrofolate.

Methotrexate may become toxic to a person’s body and produce undesirable side effects. Some of the most common side effects include inflammation of the colon, bone marrow depression and renal failure. Inflammation of the colon often makes it difficult to eat properly.

While antifolates are designed to eliminate cancer dividing cells, folate intake will not counteract the drug. The folate supplement will be depleted rapidly by the cancerous cells. Methotrexate is used to treat lupus, rheumatoid arthritis, schleroderma, psoriasis, sarcoidosis, asthma, polymyositis, and inflammatory bowel disease.

Precautions when taking Vitamin B9

Consuming excessive amounts of folic acid daily may pose some serious side effects. The Recommended Daily Allowance (RDA) is 400 micrograms per day for non-pregnant individuals. Pregnant women should consume between 600 and 800 micrograms per day. An excessive amount translates between 5,000 to 10,000 micrograms per day.

Consuming excessive amounts of B9 may mask a B12 deficiency. For this reason, some experts suggest consuming vitamin B12 in conjunction with vitamin B9. In 2007, scientists proved that vitamin B9 in excess makes the effects of a vitamin B12 deficiency worse by inhibiting its absorption rates. The excessive consumption may lead to nerve damage. These instances are rare. In most cases, the side effects are minimal. Consult a physician or go to an emergency room if the patient experiences negative side effects.

Vitamin B9 is water soluble; therefore, the vitamin is regularly excreted from the body through urine. Some research also suggests that folic acid consumed in excess may also interfere with anti-malarial treatments.

Allergic Reactions

Some individuals experience allergic reactions from folic acid intake. Individuals who are prone to allergic reactions should consult their physician prior to consuming folic acid.

Some of the symptoms may include the following:

Breathing difficulties

Rash

Itching

Swelling

Dizziness

Individuals who experience these symptoms should seek the guidance of a physician if the problems become severe. One study involving 8083 subjects found that atopy, wheezing, and asthma were related to the dosage levels given to the patients.

Folic acid taken after in vitro fertilization may improve chances of producing twins.

Role in Biological Processes

Biologically, the folic acid process in the body begins by forming tetrahydrofolate from folate. Folate reduces to dihydrofolate, which then forms tetrahydrofolate (THF). This process is catalyzed by dihydrofolate reductase. NADPH also assists in the synthesis. Methylene-Tetrahydrofolate (CH2FH4) is formed from THF by adding a methylene from a carbon donor. The carbon donor may be serine, glycine or formaldehyde. Vitamin B12 is the only acceptor of methyl-THF. Additionally, homocysteine is the only acceptor for methyl-B12. Since Vitamin B12 defiencies are often masked by vitamin B9, it is important to understand how homocysteine plays a role in the biological process of these vitamins.

Folic Acid Use Around the World

Australia

Australia and New Zealand have decided to fortify foods with folic acid. Folic acid has been included in the flour since 2009. The Food Standards Australia New Zealand regulates the process. The countries have agreed to add 0.135 mg of folic acid per 100 g of bread. The two countries debated over its inclusion before adding the beneficial vitamin.

Canada

Canada has fortified their food supply since 1998 with a synthetic form of folic acid called pteroylmonoglutamate. Canada includes 150 micrograms of folic acid per 100 grams of enriched flour or cereal. In 2003, the University of Toronto released a study indicating that the fortification movement has dramatically decrease neuroblastoma and congenital heart defects. After a study conducted by McGill University in 2009, experts noticed a 6.2 percent decrease per year in infants born with congenital heart defects.

New Zealand

Though New Zealand and Australia agreed jointly to include folic acid in a fortification plan in 2009, the country has since decided to wait until more research is conducted. New Zealand is against fortification citing it as mass medication. The country is afraid of overconsumption of folic acid and its effects.

United Kingdom

The United Kingdom is currently debating the inclusion of folic acid in bread and flour. The Food Standards Agency recommended the fortification, but the inclusion has not been mandated to date.

United States

According to the Center for Disease Control in Atlanta, GA, the number of neural tube defects has decrease 25 percent since the mandatory introduction of folic acid into the diet. Because the results remain positive, the United States Public Health Service is urging people to consume an extra 0.4 mg per day in supplement form. Since most of pregnancies are unplanned, this will reduce the risk of defects in infants.